A wide variety of medical treatments require regulation of the immune response in a patient. Such treatments include, for example, vaccinations, treatments for autoummune diseases, immunodeficiency diseases, immunoproliferative diseases and treatments involving the transplantation of organs and skin. Traditional reagents and methods used to regulate a subject's immune response often results in unwanted side effects. For example, immunosuppressive reagents such as cyclosporin A, azathioprine and prednisone are used to suppress the immune system of a patient with an autoimmune disease or patients receiving transplants. Such reagents, however, suppress a patient's entire immune response, thereby crippling the ability of the patient to mount an immune response against infectious agents not involved in the original disease. Due to such harmful side effects and the medical importance of immune regulation, reagents and methods to regulate specific parts of the immune system have been the subject of study for many years.
Introduction of an antigen into a host initiates a series of events culminating in an immune response. In addition, self-antigens can result in immunological tolerance or activation of an immune response against self-antigens. A major portion of the immune response is regulated by the interaction of a stimulator cell (defined in detail below) with a responding cell (defined in detail below).
Particular reagents having immunoregulatory potential of cell to cell interactions have been suggested by various investigators. Tykocinski et al. disclose in U.S. Pat. No. 5,242,687, issued Sep. 7, 1993, a composition comprising a CD8 peptide associated with a secondary ligand, including an Fc domain of immunoglobulin or a major histocompatibility molecule (MHC). Tykocinski et al. do not teach or suggest such a composition involving CD4, CD2, CD28, CTLA4 or fas-ligand proteins which are known to have significantly different functions in various immunity mechanisms.
In U.S. Pat. No. 5,336,603, issued Aug. 9, 1994, Capon et al. disclose "immunoadhesons" useful for immunomodulatory therapy. Capon et al. disclose adhesons as cell surface polypeptides, examples of which include CD8, CD4 and CD2, that can be combined with an immunologically active non-adheson polypeptide. Capon et al., however, do not teach or suggest a T cell veto molecule useful for immunosuppression and particularly a molecule that prevents the specific activation of responding cells by stimulator cells to suppress an immune response.
As such, there remains a need for therapeutic reagents and strategies that suppress an immune response in a safe and effective manner.